Notes

Effects of Natalizumab Treatments upon Intrathecal Immunoglobulin G Generation Suggest Targeting of Plasmablasts.
Disrupted sleep through sleep deprivation or sleep fragmentation has previously been shown to impair cognitive processing. Nevertheless, limited studies have examined the impact of disrupted sleep on the processing of emotional information. The current study aimed to use an experimental approach to generate sleep disruption and examine whether SD and SF in otherwise healthy individuals would impair emotional facial processing. Thirty-five healthy individuals participated in three-day/two-night laboratory study which consisted of two consecutive overnight polysomnograms and cognitive testing during the day. The first night was an adaptation night of normal sleep while the second was an experimental night where participants underwent either a night of 1) normal sleep, 2) no sleep (SD) or 3) fragmented sleep (SF). The emotional Go/No-Go task was completed in the morning following each night. Data from 33 participants (14 females, mean age = 24.6 years) were included in the final analysis. Following a night of SD or SF, participants performed significantly poorer with emotional (fearful and happy) targets, while no significant changes occurred after a night of normal sleep. Further, sleep deprived individuals experienced additional impairments with notably poorer performance with neutral targets and slower reaction time for all targets, suggesting an overall slowing of cognitive processing speed. These findings suggest that facial recognition in socio-emotional contexts may be impaired in individuals who experience disrupted sleep.Bipolar disorder (BD) effects on cognition are confounded by the putative cognitive impact of its major pharmacological treatments, given the neurotrophic potential of mood stabilizers, particularly lithium. We examined the area of cognitive flexibility (CF), aiming to disentangle BD from medication effects, using translational methodology. CF was assessed by CANTAB-IED (intra- extra-dimensional shift; Study 1, euthymic BD participants) and its animal analog (Study 2, rats). Both studies included groups (1) control, (2) lithium, chronic, current treatment (LI-CHRON-C, A > 2 years, N = 32; B 2 months, N = 11); (3) valproate, chronic, current treatment (VPA-CHRON-C, A > 2 years, N = 30; B 2 months, N = 12). Study 2 included 2 additional groups; Group 4 LI-CHRON-PAST (2 months, stopped 1 month pretest, N = 13); Group 5 LI-ACUTE (LI on test days only, N = 13). In Study 1, neither total nor stage (discrimination D; reversal R; intra- extra-dimensional shifts IED) IED errors differed between groups [Kruskal-Wallis H(2, N = 94) 0.95 > p > 0.65]. Similarly in Study 2, errors did not differentiate the 5 pharmacological groups. Differences emerged only between LI-ACUTE and Controls in response latencies (D, R, IED ANOVAS 0.002 > p > 0.0003; contrasts D, R p = 0.002, 0.0001). In conclusion, LI and VPA BD patients were indistinguishable from Controls in IED errors, as were animals treated with LI-CHRON, current or past, or VPA-CHRON-C vs Controls. LI-ACUTE treatment produced significant latency deficits vs Controls. Within the limitations of translational comparisons, our results suggest that the normal CF noted in euthymic BDs is not attributable to mood stabilizer effects.
With the emergence of evidence-based treatments for treatment-resistant depression, strategies to identify individuals at greater risk for treatment resistance early in the course of illness could have clinical utility. We sought to develop and validate a model to predict treatment resistance in major depressive disorder using coded clinical data from the electronic health record.

We identified individuals from a large health system with a diagnosis of major depressive disorder receiving an index antidepressant prescription, and used a tree-based machine learning classifier to build a risk stratification model to identify those likely to experience treatment resistance. The resulting model was validated in a second health system.

In the second health system, the extra trees model yielded an AUC of 0.652 (95% CI 0.623-0.682); with sensitivity constrained at 0.80, specificity was 0.358 (95% CI 0.300-0.413). Lift in the top quintile was 1.99 (95% CI 1.76-2.22). Linsitinib in vivo Including additional data for the 4 weeks following treatment initiation did not meaningfully improve model performance.

The extent to which these models generalize across additional health systems will require further investigation.

Electronic health records facilitated stratification of risk for treatment-resistant depression and demonstrated generalizability to a second health system. Efforts to improve upon such models using additional measures, and to understand their performance in real-world clinical settings, are warranted.
Electronic health records facilitated stratification of risk for treatment-resistant depression and demonstrated generalizability to a second health system. Efforts to improve upon such models using additional measures, and to understand their performance in real-world clinical settings, are warranted.
Depression is a treatable disease, and untreated depression can lead to serious health complications and decrease the quality of life. Therefore, prevention, early identification, and treatment efforts are essential. Screening has an essential role in preventive medicine in the general population. Ideally, screening tools detect patients early enough to manage the disease and reduce symptoms. We aimed to determine the cost-effectiveness of routine screening schedules.

We used a discrete-time nonstationary Markov model to simulate the progression of depression. We used Monte Carlo techniques to simulate the stochastic model for 20 years or during the lifetime of individuals. Baseline and screening scenario models with screening frequencies of annual, 2-year, and 5-year strategies were compared based on incremental cost-effectiveness ratios (ICER). Monte Carlo (MC) simulation and one-way sensitivity analysis were conducted to manage uncertainties.

In the general population, all screening strategies were cprevention efforts can be one critical cornerstone to support required care. Our analysis combined the expected benefits and costs of screening and assessed the effectiveness of screening scenarios. We conclude that routine screening is cost-effective for all age groups of females and young, middle-aged males.
Major depressive disorder (MDD) with non-suicidal self-injury (NSSI)(MDD/NSSI) has been found to differ from simple MDD without NSSI (sMDD). This study analyzes the amplitude of low-frequency fluctuations (ALFF) to explore the NSSI-relevant local neural activity, and uses functional connectivity (FC) analysis to explore the NSSI-relevant circuits corresponding to alterations in local regions in young adult patients with MDD/NSSI.

A total of 54 patients with MDD/NSSI, 68 patients with sMDD, and 66 matched healthy controls (HCs) were recruited. ALFF and seed-based FC analyses were employed. The NSSI-relevant brain alteration and its associations with clinical variables were examined.

Compared with the sMDD group, the MDD/NSSI group showed higher ALFF in the right lingual gyrus and right middle occipital gyrus; lower ALFF in the right superior frontal gyrus; higher FC values between the right lingual gyrus and left precentral gyrus; and lower FC values between the right middle occipital gyrus and right paracentral gyrus. Within the MDD/NSSI group, ALFF values of the right superior frontal gyrus and right lingual gyrus were positively correlated with the frequency and severity of NSSI.

The sample size was small, and the potential influence of medicine on brain activity was not excluded.

Our preliminary findings indicate that NSSI-relevant ALFF in the right lingual gyrus, right middle occipital gyrus, and right superior frontal gyrus, as well as the alteration FCs in corresponding brain circuits, may play an important role in the neural basis of MDD/NSSI.
Our preliminary findings indicate that NSSI-relevant ALFF in the right lingual gyrus, right middle occipital gyrus, and right superior frontal gyrus, as well as the alteration FCs in corresponding brain circuits, may play an important role in the neural basis of MDD/NSSI.
Recent studies demonstrate substantial effects of deceptive placebo on experimentally induced sadness, even on autonomic activity. Whether deception is necessary, remains to be elucidated. We investigated the effect of an open-label placebo (OLP) treatment, i.e. an openly administered placebo delivered with a convincing rationale for its sadness-protecting effect.

Eighty-four healthy females were randomized to an OLP group or a no-treatment control group. All participants received the same detailed information about the OLP effect, only the OLP group received an OLP nasal spray. Before and after the OLP intervention, participants underwent a sad mood induction procedure combining self-deprecating statements (Velten's method) and sad music. Sadness was assessed by the Positive and Negative Affect Schedule (PANAS-X). Autonomic activity was measured continuously.

Participants in the OLP group reported a significantly attenuated increase in sadness upon mood induction and less sadness after induction comparociated positive treatment expectations.
Elevated aggression and impulsivity are implicated in Bipolar Disorder (BD); however, relationships between these behavioral constructs have not been clarified, which can lead to misconceptions with negative consequences including stigma and adverse outcomes including suicide. The study aimed to clarify brain-based distinctions between the two constructs and their associations to risk factors, symptoms and suicide thoughts and behaviors.

Self-rated Brown-Goodwin Aggression (BGA) and Barratt Impulsiveness Scale (BIS) scores were compared between adults with BD (n=38, 74% female) and healthy controls (HC, n=29, 64% female). Relationships were examined between BGA and BIS with childhood trauma questionnaire (CTQ), mood, comorbidities, and magnetic resonance imaging gray matter volume (GMV) assessments.

In BD, BGA and BIS total scores were both elevated and associated with childhood maltreatment (CM), particularly emotional CM, depression, substance use disorders (SUDs) and suicide attempts (SAs). BGA scoreed. Both domains are associated with suicide behavior and modifiable risk factors of CM, depression and SUDs that could be targeted for prevention.
Predominant polarity (PP) is a concept used to define patients with bipolar disorder (BD) as presenting a tendency to manifest depressive (DPP) or manic (MPP) episodes. Still, the high percentage of patients with an undetermined PP (UPP), has been overlooked in most studies. Thus, we aimed to study UPP and outline its socio-demographic, clinical, and treatment-related features.

Patients were recruited from a BD specialized unit. The sample was divided into three groups according to PP and socio-demographic and clinical variables were compared. Significant variables at univariate comparisons were included in multivariate logistic regression with UPP as the dependent variable.

A total of 708 BD patients were included, of which 437 with UPP (61.7%). UPP was associated with a higher number of affective relapses, when compared with DPP or MPP (χ2= 28.704, p<0.001). Mixed episodes (OR=1.398; CI=1.118-1.749), aggressive behaviour (OR=1.861; CI=1.190-2.913), seasonality (OR=2.025; CI= 1.289-3.501) and treatment with lamotrigine (OR= 2.
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